Main outcome measures: Frequency and Poisson regression analyses for trend of reported causes of bacteraemia and proportions of antibiotic resistant isolates.

Results: There was an upward trend in total numbers of reports of bacteraemia. The five most cited organisms accounted for over 60% of reports each year. There was a substantial increase in the proportion of reports of Staphylococcus aureus resistant to methicillin, Streptococcus pneumoniae resistance to penicillin and erythromycin, and Enterococcus faecalis and Enterococcus faecium resistance to vancomycin. No increase was seen in resistance of Escherichia coli to gentamicin.

Conclusions: Reports from laboratories provide valuable information on trends and antibiotic resistance in bacteraemia and show a worrying increase in resistance to important antibiotics.

Editorial by Amyes

Introduction

Culture of blood is a fundamental investigation in infection. Illness associated with bacteraemia ranges from self limiting infection to life threatening sepsis that requires rapid and aggressive antimicrobial treatment,1 which is complicated by increasing antibiotic resistance worldwide.2–5 Information on trends and antibiotic resistance in bacteraemia is needed to inform prescribing and infection control policy and to guide development of new antibiotics and vaccines.13–7

Since 1989 blood isolates judged to be clinically significant by microbiologists working in laboratories in England and Wales have been reported to the Public Health Laboratory Service Communicable Disease Surveillance Centre; this moved from paper to electronic transmission with EpiBase8 then CoSurv.9 Trends in resistance to key antibiotics have been published for Staphylococcus aureus, 1011Streptococcus pneumoniae,12 andEscherichia coli. 13 Here we present the first overall description of the system and causative organisms with further information on antibiotic resistance.

Methods

Blood isolates reported to the surveillance centre from 1990 to 1998 were entered on a computer database (LabBase).8 Replicate reports were identified by matching on date of birth, sex, specimen date, organism, antibiotic susceptibility, and source laboratory and merged if the specimen dates were less than eight days apart. This was undertaken manually from 1990 to 1994 and then by computer program.

We identified laboratories in England and Wales that reported blood isolates to the surveillance centre in 1998 from the Directory of the Association of Medical Microbiologists.14 Annual total bacteraemias and annual counts for each of 34 “categories” of bacteraemia defined by causative organism15 were analysed by Poisson regression analysis.16 Categories showing a year on year proportional increase were further analysed within age groups. The causes of bacteraemia between age groups were examined. Trends in the proportion resistant were determined for the subset of reports with a completed antibiotic susceptibility field. Intermediate resistance was recorded in less than 0.7%of reports and was counted as resistance.

Results

Of 229 laboratories identified in England and Wales in the directory,14 208 (91%) reported blood isolates to the surveillance centre in 1998. Reports increased from 31 763 in 1990 to 51 232 in 1998(P<0.05)(fig 1). E coli, Staph aureus, coagulase negative staphylococci, Strep pneumoniae, and either Enterococcus species (includingE faecium, E faecalis, and group D streptococci) or Klebsiella species (fig 1) accounted for 60% of all reports each year. A further 20% comprised either Klebsiella species orEnterococcus species, γ and non-haemolytic streptococci (other than pneumococci), and Proteus species, Enterobacter species, and Pseudomonas aeruginosa.

Fig 1

Incidence of commonly reported causes of bacteraemia in England and Wales, 1990 to 1998

Poisson regression showed a year on year proportional increase for seven categories (table 1) that was also present within each age group. Haemophilus influenzae declined steeply from 1992. Most reports were from adults but the reporting rate was high in infants: 1149 reports for infants aged 0-28 days and 1169 for infants aged 29 to 365 days in 1998 (table 2).

Table 1

Causative organisms of bacteraemia, showing year on year proportional increasing trend by Poisson regression analysis, 1990-8

Numbers of reports of bacteraemia and report rate per 100000 by age group in England and Wales, 1998. Denominators for rates were mid-year population estimates for England and Wales (Office for National Statistics, London)

Staph aureus was among the top five causes of bacteraemia in every age group, whereas E coli, coagulase negative staphylococci, Strep pneumoniae, and Enterococcus species ranked lower at certain ages (fig 2). γ and non-haemolytic streptococci (excluding pneumococci) accounted for 5-7% of bacteraemias in children of all ages and for 2-4% aged over 14 years. Group B streptococci comprised 22% of reports in infants aged 0 to 28 days, 5% in infants aged 29 days to 1 year, were rare in children aged between 1 and 14 years (three reports in 1998), but contributed 1-2% in the adult age groups. Neisseria meningitidis accounted for 11-17% of reports in age groups from birth to 14 years, 2% from 15 to 44 years, and less than 1% in older age groups. The proportion of reports contributed by each age group to each category of bacteraemia was similar in every year.

Fig 2

Common causes of bacteraemia by age group as proportion of total reports for England and Wales, 1998 (age group <1 month equals ≤28 days; 1-11 months equals 29-365 days)

The subset of reports with completion of the antibiotic susceptibility field generally declined in 1996 and 1997 and recovered in 1998 (fig 3). Methicillin resistance in Staph aureus increased from 1.7% to 3.8% from 1990 to 1993, rose steeply to 32% in 1997 and to 34% in 1998 (fig 3). Gentamicin resistance inE coli increased from 1.7% in 1990 to 3% in 1997 declining to 2.2% in 1998. Vancomycin resistance in Ent faecium reached 6.3% in 1993, 20% in 1995, and 24% in 1998. Vancomycin resistance in Ent faecalis was under 3% from 1990 to 1996, increasing to 5% in 1998. Ampicillin resistance, however, was recorded in 15% of Ent faecalis and ampicillin sensitivity in 17% of Ent faecium reports in 1998, suggesting frequent mis-speciation. Penicillin resistance inStrep pneumoniae was under 1% in 1990 and 1991, increasing to 3.7% in 1996, to 7.4% in 1997, and 3.6% in 1998. Erythromycin resistance in Strep pneumoniae increased from 5% in 1990 to stabilise at about 11% from 1994 onwards.

Discussion

The number of reports increased yearly; a steep increase between 1996 and 1998 (fig 1) coincided with efforts to encourage reporting, including “free” installation of CoSurv9 into laboratories, but the number bearing data on antimicrobial susceptibility did not increase except for methicillin againstStaph aureus(fig 3). This was probably due to problems in the introduction of CoSurv and different degrees of effort in chasing up missing results for each antimicrobial susceptibility. Increased reporting may also have reflected rising incidence due to improved survival of severely ill patients.1718

What is already known on this subject

Bacteraemia series from laboratories and programmes of nosocomial infection surveillance are generally derived from individual or small numbers of institutions

The collated data may be unrepresentative of the general population and inferences may lack precision because of the small number of reports

The need for representative and precise information on the causes and trends in antibiotic resistance in blood stream infections at national level made an overview of the system desirable at this time

What this paper adds

Over 90% of laboratories in England and Wales reported clinically significant blood isolates to the communicable disease surveillance centre in 1998, with total reports ranging from about 30 000 in 1990 to 50 000 in 1998

This reporting system probably captures information on a sizeable proportion of episodes of bacteraemia at national level

The value of this system for national level monitoring of antibiotic resistance and trends in the causes of bacteraemia has been demonstrated; regional analyses with multivariable methods may prove useful in the future

The causes of bacteraemia were similar to those seen in other large series.17–19 Categories with a marked upward trend (table 1) are a priority for further research. The trend forCorynebacterium species and diphtheroids may reflect a change from regarding these organisms as skin contaminants to being clinically significant, as occurred for coagulase negative staphylococci.20 Marked increases inAcinetobacter species, Serratia species, Citrobacter species, and Enterobacter species may reflect their facility to develop mutational resistance to cephalosporin antibiotics, which were used increasingly during the survey period. We found no shift to Gram positive organisms as reported elsewhere.117–20 This may have occurred before the study period or be specific to certain patient groups, such as patients with neutropaenia. The fall in H influenzae followed introduction of Hib immunisation in 1992.21

The rise in antibiotic resistance in blood isolates emphasises the importance of sound hospital infection control,67 rational prescribing policies, and the need for new antimicrobial drugs and vaccines.3–5 Validation of reported data on resistance has been undertaken by comparison with centralised testing of nationally representative sample strains.13 Regional analyses have been developed for methicillin against Staph aureus22 (http://www.phls.co.uk/facts/bact.htm). Further analysis of these data could include the determination of the independent effect on antibiotic resistance of region, year, age, and sex by using multivariable methods.16 This national reporting system should complement local surveillance of bacteraemia in which extensive data on risk factors may be collected.2324

Acknowledgments

We thank the microbiology laboratory staff in England and Wales for reporting isolates to the surveillance centre.

Contributors: MHR designed and coordinated the study, supervised the downloading and analysis of data, and wrote the paper. AS retrieved and processed data. DML advised on the design of the study and reviewed and contributed to writing the paper. MCJW advised on the design of the study and reviewed the paper. CG undertook the statistical analyses. APJ contributed to the design of the project and reviewed the paper. HH advised and assisted in the retrieval of data and reviewed the paper. MAM and KFB developed the routine bacteraemia reporting system, which provided the framework for this paper, and each reviewed the paper. DJ monitored the completeness of antibiotic susceptibility reporting and chased up missing data. RCG advised on design of the project and reviewed the paper. MHR, DML, and HH are guarantors for the paper.